Our goal is to gain further knowledge of the secretory immune system so as to enhance prospects for effective elicitation of secretory IgA antibody responses as immunoprophylaxis against infectious agents and environmental carcinogens. The general outlines of the differentiation pathways and routes of cell traffic in the secretory immune system are now understood, but there is no information on the specific mechanisms involved. We now want to develop homogeneous cell populations with which to study cell homing to exocrine sites in more detail. Three kinds of cells will be evaluated: surface IgA-positive cells isolated from normal mesenteric nodes by a fluorescence-activated cell sorter; the products of fusion of surface IgA-positive precursor cells in mesenteric nodes with nonproducing myeloma cells; and newly induced IgA plasmacytomas. The cells to be tested will be radiolabeled, injected intravenously and evaluated for tropism toward mucosal-associated lymphoid tissue. After obtaining cells with the desired homing characteristics, we shall seek to identify in milk or in culture supernatants from mammary carcinomas a chemotactic factor that accounts for trapping of IgA-producing cells in exocrine sites. If this is successful, we shall attempt to purify the factor. In studies of the synthesis, assembly and transport of secretory IgA, we shall attempt to develop an in vitro system in which a purified disulfide interchange enzyme promotes the formation of secretory IgA from pure components. Enzymes from different tissue sources will be compared both structurally and functionally, and the enzyme will be localized within cells by means of immunoelectron microscopy. Its localization will be compared with that of secretory component in dormant intestinal epithelial cells in culture and in cells which are transporting IgA. Finally, we shall attempt to develop an animal model of IgA nephropathy by prolonged oral immunization with specific antigen, with or without supplementary antigen given parenterally.